Every child that develops a diffuse intrinsic pontine glioma (DIPG) dies within a year of diagnosis. About 300 children 10 and younger develop this type of tumor each year. Scientists at Northwestern Medicine have identified a molecule that stops the growth of this aggressive brain tumor.
DIPG tumors are in the deepest area of the brain, called the brainstem, in a region called the pons. The brainstem sits just above the back of the neck and is connected to the spine. The pons regulates many important bodily functions such as breathing, blood pressure and heart rate.
DIPG arises from cells in the brain called glia, which are the cells that support the neurons responsible for thought, memory and movement. There are roughly three times as many glia as neurons in the brain. One of the main functions of glia is to provide the myelin covering neurons. Myelin acts as insulation and speeds up the transmission of signals along the nerves.
Symptoms of DIPG include difficulties with balance, poor vision, nausea and vomiting, headaches and facial drooping. Diagnosis is usually made by MRI imaging, and the tumors are rarely biopsied or removed because of the tumor’s location deep in the brain. Radiation therapy and chemotherapy are used to treat DIPG, but they only prolong survival by a few months. There is no cure for DIPG.
The DNA that contains all our genetic information is packaged into the nucleus of our cells. This packaging includes wrapping the DNA around a structure consisting of proteins called histones. The mutation that begins this cancer is thought to be in a histone called H3. The mutation prevents a protein complex called PRC2 from doing its job to control the utilization of other genes. Without PRC2 controlling certain genes, DIPG tumors develop.
PRC2 functions on undifferentiated cells, which are stem cells that can grow into many different types of cells. Undifferentiated cells are generally the most aggressive types of tumors.
To test the hypothesis that PRC2 activity is important in DIPG tumors, the scientists developed a molecule called JQ1 that binds to and inhibits the activity of PRC2. This drug is similar to a group of drugs called BET inhibitors, which are being tested as treatments for pediatric leukemias and other tumors. This molecule was added to petri plates of DIPG tumor cells and found to inhibit their growth and make them look more normal.
Encouraged by these results, the scientist recreated DIPG tumors by injecting human tumor cells into the brainstems of mice. After the mice developed tumors, they were treated with JQ1 for 10 days, which resulted in a dramatic reduction in tumor size and substantially prolonged their survival. The tumor cells looked more normal after the treatment.
Though still in lab testing, this offers the first hope to DIPG patients that there could be drugs on the horizon to treat this type of tumor and perhaps make this tumor survivable. Let’s hope so.